In vivo toxicological evaluation of polymeric nanocapsules after intradermal administration.

Polymeric nanocarriers have shown great promise as delivery systems. An alternative strategy has been to explore new delivery routes, such as intradermal (i.d.), that can be used for vaccines and patch-based drug delivery. Despite their many advantages, there are few toxicity studies, especially in vivo. We report a safety assessment of biodegradable poly(ɛ-caprolactone) lipid-core nanocapsules (LNC) with a mean size of 245±10nm following single and repeated intradermal injections to Wistar rats. Suspensions were prepared by interfacial deposition of polymer. The animals (n=6/group) received a single-dose of saline solution (1.2ml/kg) or LNC (7.2×10(12)LNC/kg), or repeated-doses of two controls, saline solution or Tween 80 (0.9ml/kg), or three different concentrations of LNC (1.8, 3.6, and 5.4×10(12)LNC/kg) for 28 consecutive days. Clinical and physiological signs and mortality were observed. Samples of urine, blood, and tissue were used to perform toxicological evaluation. There were no clinical signs of toxicity or mortality, but there was a slight decrease in the relative body weights in the Tween 80-treated group (p<0.01) after repeated administration. No histopathological alterations were observed in tissues or significant changes in blood and urinary biomarkers for tissue damage. Mild alterations in white blood cells count with increases in granulocytes in the Tween-80 group (p<0.05) were found. Genotoxicity was evaluated through the comet assay, and no statistical difference was observed among the groups. Therefore, we conclude that, under the conditions of these experiments, biodegradable LNC did not present appreciable toxicity after 28 consecutive days of intradermal administration and is promising for its future application in vaccines and patch-based devices for enhancing the delivery of drugs.

Blood thioredoxin reductase activity, oxidative stress and hematological parameters in painters and battery workers: relationship with lead and cadmium levels in blood.

Oxidative stress has been shown to be involved in lead and cadmium toxicity. We recently showed that the activity of the antioxidant enzyme thioredoxin reductase (TrxR) is increased in the kidneys of lead-exposed rats. The present study evaluated the blood cadmium and blood lead levels (BLLs) and their relationship with hematological and oxidative stress parameters, including blood TrxR activity in 50 painters, 23 battery workers and 36 control subjects. Erythrocyte δ-aminolevulinate dehydratase (δ-ALA-D) activity and its reactivation index were measured as biomarkers of lead effects. BLLs increased in painters, but were even higher in the battery workers group. In turn, blood cadmium levels increased only in the painters group, whose levels were higher than the recommended limit. δ-ALA-D activity was inhibited only in battery workers, whereas the δ-ALA-D reactivation index increased in both exposed groups; both parameters were correlated to BLLs (r = -0.59 and 0.84, P < 0.05), whereas the reactivation index was also correlated to blood cadmium levels (r = 0.27, P < 0.05). The changes in oxidative stress and hematological parameters were distinctively associated with either BLLs or blood cadmium levels, except glutathione-S-transferase activity, which was correlated with both lead (r = 0.34) and cadmium (r = 0.47; P < 0.05). However, TrxR activity did not correlate with any of the metals evaluated. In conclusion, blood TrxR activity does not seem to be a good parameter to evaluate oxidative stress in lead- and cadmium-exposed populations. However, lead-associated changes in biochemical and hematological parameters at low BLLs underlie the necessity of re-evaluating the recommended health-based limits in occupational exposure to this metal.

Main lepidopteran pest species from an eucalyptus plantation in Minas Gerais, Brazil.

Lepidoptera species were monitored in a plantation of Eucalyptus grandis in the Municipality of Bom Despacho, State of Minas Gerais, Brazil from March 1987 to February 1992. A total of 547 species were collected and divided in: primary pests: 13; secondary pests: 20; species without defined importance to eucalyptus: 79; and non-identified species: 435. These four groups had a mean of 5231.29; 338.18; 438.16 and 2222.87 individuals with a total of 8229.87 individuals collected per trap. The number of species without defined importance to eucalyptus, and non-identified species, increased during the collecting period of five years while those of primary and secondary pests showed similar numbers in all years. The most collected primary pests Thyrinteina arnobia Stoll and Stenalcidia sp. (Geometridae) showed higher frequencies during the driest and coldest periods of the year, whereas Psorocampa denticulata Schaus (Notodontidae) was most frequent during periods of higher rainfall. Species of groups III and IV increased in diversity with eucalyptus age. This area has a high probability of outbreaks of eucalyptus defoliating caterpillars, especially T. arnobia. For this reason, lepidopteran pests should be monitored in this plantation during the driest and coldest periods of the year, when they can reach population peaks.